Bioinspired Self-assembled Nanoparticles for the Delivery of Therapeutics

Biological therapeutics, such as the emerging nucleic acid based drugs (siRNA, miRNA, and mRNA) and heparin-binding (HB) proteins for tissue regeneration and repair have proven to be therapeutically effective in preclinical studies. Yet, their clinical translation as therapeutics has been limited due to the use of supraphysiological dosages, thus increasing the risk for systemic toxicity. Delivery of these biological therapeutics in nanoparticles (NPs) could potentially reduce the dosage required to achieve therapeutic efficacy and improve their clinical outcome. Herein, I will describe the features of novel, slightly anionic and biocompatible nanoparticles (NPs), spontaneously co-assembled due to electrostatic interactions. The NPs efficiently encapsulate and protect the biological therapeutics from enzymatic degradation. Injection of a combination of NPs encapsulating multiple therapeutic growth factors (all HB proteins) promoted effective and long-term tissue repair in animal models of severe ischemia (hindlimb ischemia and myocardial infarction). Further, we demonstrate that after intravenous administration, NPs entrapping siRNA and miRNA could be targeted to specific diseased tissues, such as to cardiac macrophages in infarcted hearts. This simple yet efficient NP fabrication method has demonstrated versatility to various biological therapeutics and is amenable for clinical use. I will present our attempts to implement the technology in large animal models as well as our collaboration with Industry.